Antibacterial Agents
IABLE
Antibiotics Antibacterial Agents

Antibacterial Agents

Most antibacterial agents are considered compatible with lactation and are not an indication to pump and dump. In general, it is reasonable to monitor breastfed infants for gastrointestinal side effects such as diarrhea, thrush, diaper rash, or blood in the stool while their lactating parent is on an antibiotic. Only antibacterial agents with special considerations during lactation are outlined in this section. Many currently available antibiotics, such as penicillins and cephalosporins, are generally considered safe during lactation.

For more detailed information and references on specific medications, please refer to LactMede-lactanciaInfant Risk, or Mother to Baby.

Trimethoprim-Sulfamethoxazole/Bactrim

Trimethoprim-sulfamethoxazole has relatively low milk transfer compared to infant weight-based dosing.1 Additionally, no reports of jaundice related to the use of trimethoprim-sulfamethoxazole were found in a systematic review of the literature.2 However, there is a theoretical risk of jaundice among breastfed infants who are at highest risk, so caution may be warranted and alternatives should be considered in specific populations, including neonates under 8 days old, premature infants, stressed or ill infants, and jaundiced infants. This agent should be avoided in lactating parents of G6PD-deficient infants.3 While there is no absolute indication to pump and dump, shared decision making should be utilized in certain special groups of infants with risk factors for jaundice. Alternative medications are preferred for lactating parents of G6PD-deficient infants and other at risk infants, including preterm infants or newborns with hyperbilirubinemia.

Dapsone

Dapsone has limited data in lactation. It appears to readily enter breast milk. There is a case report of hemolytic anemia in a newborn likely due to exposure to dapsone through breastmilk.4 Hemolytic anemia may occur with the use of this medication, especially in  full-term or preterm newborns  and in those with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Therefore, systemic Dapsone should be used with caution in lactating parents with shared decision making and close monitoring of the infant for signs of hemolytic anemia. Alternative medications are preferred for lactating parents of G6PD-deficient infants and other at risk infants, including preterm infants or newborns with hyperbilirubinemia.

Fluoroquinolones

Systemic Fluoroquinolones

Commonly used systemic fluoroquinolones include ciprofloxacin/Cipro and levofloxacin/Levaquin. There is one case report of pseudomembranous colitis in an infant of a mother who self-treated with ciprofloxacin at unclear doses.5 However, levels of ciprofloxacin and levofloxacin excreted in human milk at usual maternal doses are relatively low and breastfed infant plasma levels are undetectable or very low with the use of levofloxacin.6 There is no absolute indication to pump and dump with the use of oral fluoroquinolones at prescribed doses.

Topical Fluoroquinolones

Commonly used topical fluoroquinolones include otic ofloxacin/Floxin Otic and ophthalmic ofloxacin/Ocuflox. When used topically, exceedingly low maternal plasma levels are expected and these medications are unlikely to enter breastmilk in significant amounts. There is no absolute indication to pump and dump with topical otic or ophthalmic use.

Macrolides

Macrolide antibiotics include erythromycin and azithromycin/Zithromax.

Erythromycin

An association between certain macrolides, including erythromycin, and the incidence of pyloric stenosis has been described in a cohort study.7 There is one case report of a 3 week old, breastfed infant developing pyloric stenosis after exposure to this medication via breastmilk.8 While direct erythromycin exposure given to newborns is a risk factor for the development of pyloric stenosis, two larger recent meta-analyses have not found a link between erythromycin exposures via breastmilk and pyloric stenosis.9,10 While erythromycin should be used with caution in lactating parents of newborns, with close monitoring for symptoms of pyloric stenosis (such as forceful vomiting), there is no absolute indication to pump and dump and providers should engage lactating individuals in shared decision making with the use of erythromycin.

Azithromycin/Zithromax

There are no reports of adverse events in breastfed infants per LactMed and more recent meta-analyses did not show a link between macrolide use and pyloric stenosis.9,10 There is no absolute indication to pump and dump.

Metronidazole/Flagyl

While relative infant dose (RID) is > 10% for intravenous and oral metronidazole during lactation, doses are lower than treatment doses used in infants. Although LactMed notes a few case reports of adverse events in breastfed infants including diarrhea with possible development of lactose intolerance and oral thrush, several small studies found no adverse effects in infants exposed to metronidazole via breastmilk. One study found one case of oral thrush in an infant and increased Candida colonization in infants exposed to metronidazole, but this did not reach statistical significance. This study’s authors concluded that there were not significant adverse effects to infants exposed to metronidazole in human milk.11 While there is no absolute indication to pump and dump, parents should be engaged in shared decision making with the use or oral metronidazole and infants should be closely monitored for possible side effects.

Topical and intravaginal metronidazole have not been studied during lactation. However, peak plasma levels are 1% after topical application and 2% after intravaginal application. Water-miscible creams or gels are preferred if topical metronidazole is used on the breast as ointments may expose the infant to higher levels of mineral paraffins via oral exposure to the infant.12 There is no absolute indication to pump and dump with topical and intravaginal application of metronidazole.

Nitrofurantoin/Macrobid

Nitrofurantoin/Macrobid use results in low levels of this medication in human milk. While there are no case reports of hemolytic anemia among breastfed infants, infants under 1 month of age and infants with G6PD deficiency are at risk of hemolysis when they are directly given nitrofurantoin. While there is no absolute indication to pump and dump, alternatives are preferred in lactating parents of G6PD-deficient infants and other at risk infants, including preterm infants or newborns with hyperbilirubinemia.

Tetracyclines

Tetracyclines (tetracycline, doxycycline, minocycline/Minocin, tigecycline/Tigacyl) carry a risk of dental staining and bone deposition if given directly to infants and young children. Per LactMed, available literature suggests these medications can be used in short courses (<21 days) as milk levels are low and absorption by breastfed infants is low due to the medication binding with calcium in breastmilk. Out of an abundance of caution, longer courses or repeated treatments with tetracyclines are not recommended during lactation. While there is no absolute indication to pump and dump, limit the use of tetracyclines to  less than 3 weeks and avoid repeated use.

References

(1)          Miller, R.; Salter, A. The Passage of Trimethoprim/Sulfamethoxazole into Breast Milk and Its Significance. Daikos CK, ed. Progress in Chemotherapy. Antibacterial Chemotherapy. 1974, No. 1, 687–691.

(2)          Forna, F.; McConnell, M.; Kitabire, F. N.; Homsy, J.; Brooks, J. T.; Mermin, J.; Weidle, P. J. Systematic Review of the Safety of Trimethoprim-Sulfamethoxazole for Prophylaxis in HIV-Infected Pregnant Women: Implications for Resource-Limited Settings. AIDS Rev 2006, 8 (1), 24–36.

(3)          Chung, A. M.; Reed, M. D.; Blumer, J. L. Antibiotics and Breast-Feeding: A Critical Review of the Literature. Paediatr Drugs 2002, 4 (12), 817–837. https://doi.org/10.2165/00128072-200204120-00006.

(4)          Sanders, S. W.; Zone, J. J.; Foltz, R. L.; Tolman, K. G.; Rollins, D. E. Hemolytic Anemia Induced by Dapsone Transmitted through Breast Milk. Ann Intern Med 1982, 96 (4), 465–466. https://doi.org/10.7326/0003-4819-96-4-465.

(5)          Harmon, T.; Burkhart, G.; Applebaum, H. Perforated Pseudomembranous Colitis in the Breast-Fed Infant. J Pediatr Surg 1992, 27 (6), 744–746. https://doi.org/10.1016/s0022-3468(05)80106-x.

(6)          Cahill, J. B.; Bailey, E. M.; Chien, S.; Johnson, G. M. Levofloxacin Secretion in Breast Milk: A Case Report. Pharmacotherapy 2005, 25 (1), 116–118. https://doi.org/10.1592/phco.25.1.116.55616.

(7)          Sørensen, H. T.; Skriver, M. V.; Pedersen, L.; Larsen, H.; Ebbesen, F.; Schønheyder, H. C. Risk of Infantile Hypertrophic Pyloric Stenosis after Maternal Postnatal Use of Macrolides. Scand J Infect Dis 2003, 35 (2), 104–106. https://doi.org/10.1080/0036554021000027010.

(8)          Stang, H. Pyloric Stenosis Associated with Erythromycin Ingested through Breastmilk. Minn Med 1986, 69 (11), 669–670, 682.

(9)          Abdellatif, M.; Ghozy, S.; Kamel, M. G.; Elawady, S. S.; Ghorab, M. M. E.; Attia, A. W.; Le Huyen, T. T.; Duy, D. T. V.; Hirayama, K.; Huy, N. T. Association between Exposure to Macrolides and the Development of Infantile Hypertrophic Pyloric Stenosis: A Systematic Review and Meta-Analysis. Eur J Pediatr 2019, 178 (3), 301–314. https://doi.org/10.1007/s00431-018-3287-7.

(10)        Almaramhy, H. H.; Al-Zalabani, A. H. The Association of Prenatal and Postnatal Macrolide Exposure with Subsequent Development of Infantile Hypertrophic Pyloric Stenosis: A Systematic Review and Meta-Analysis. Ital J Pediatr 2019, 45 (1), 20. https://doi.org/10.1186/s13052-019-0613-2.

(11)        Passmore, C. M.; McElnay, J. C.; Rainey, E. A.; D’Arcy, P. F. Metronidazole Excretion in Human Milk and Its Effect on the Suckling Neonate. Br J Clin Pharmacol 1988, 26 (1), 45–51. https://doi.org/10.1111/j.1365-2125.1988.tb03362.x.

(12)        Noti, A.; Grob, K.; Biedermann, M.; Deiss, U.; Brüschweiler, B. J. Exposure of Babies to C15-C45 Mineral Paraffins from Human Milk and Breast Salves. Regul Toxicol Pharmacol 2003, 38 (3), 317–325. https://doi.org/10.1016/s0273-2300(03)00098-9.